We were among the first groups to demonstrate the profound negative effect that Mov10 has on retrovirus replication. As a cytoplasmic protein associated with P-bodies and RISC machinery, overexpression of Mov10 impairs the production of infectious HIV-1, SIV, EIAV, FIV, and MLV. Mov10 is incorporated in HIV-1 particles through an interaction that appears to be RNA dependent. We observe at least two antiviral effects by Mov10. Interestingly, an N-terminal domain of Mov10 that is not virion incorporated interferes with HIV-1 production. With Dr. Eric Freed (DRP/CCR), we are currently examining the role of Mov10 and related cytoplasmic RNA machinery in retrovirus production and infectivity. Our findings suggest that Mov10 regulation of cellular mRNAs could indirectly regulate retrovirus replication. In a related effort with Dr. Bruce Shapiro (BRL/CCR), we have examined the potency of RNA therapeutics to regulate HIV-1 replication. [Corresponds to KewalRamani Project 2 in the October 2011 site visit report of the HIV Drug Resistance Program]